Mesenchymal Stem Cells Alleviate Inflammatory Bowel Disease Via Tr1 Cells

Mesenchymal stem cells (MSCs) have been used to achieve exciting therapeutic outcomes in many animal studies and clinical trials for various autoimmune diseases, including inflammatory bowel disease (IBD). Type 1 regulatory T (Tr1) cells are the main source of interleukin (IL) 10 in the intestine. Whether Tr1 cells are involved during MSC-mediated IBD treatment is unclear. We treated a murine model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis with human umbilical cord-derived MSCs (hUCMSCs) and found that the disease severity was alleviated significantly in a dose-dependent manner. hUCMSCs increased the proportion of Tr1 cells and decreased that of T helper (Th)-1 and Th17 cells in the spleen and mesenteric lymph nodes in different stages of colitis. We found that the upregulation of Tr1 cells by hUCMSCs was abrogated after blocking indoleamine-2,3-dioxygenase (IDO), and IDO knockdown in hUCMSCs reversed the increase in Tr1 cell proportions caused by hUCMSCs in colitis. Moreover, hUCMSCs inhibited apoptosis and promoted the proliferation of Tr1 cells. Our results suggest that Tr1 cells play an important role in the amelioration of IBD by MSCs, and they are the target population for the alleviation of IBD by MSCs, providing meaningful references for the study of therapeutic mechanisms of MSCs in other inflammatory diseases.Graphical abstract